Taxol, a substance originally isolated from the Pacific Yew tree (taxus brevefolia) has recently been approved for clinical treatment of cancer patients. Recent research efforts directed to its chemical synthesis and the synthesis of taxoid model systems have been recently reviewed by Nicolaou et al., Angew. Chem. Int. Ed. Engl. 1994, 33, 15.
A convergent approach to the synthesis of the taxoid family of compounds in which a Shapiro-type coupling is used as a means of joining rings A and C has been disclosed by Nicolaou et al, J. Chem. Soc., Chem. Commun. 1993, 1017 and J. Chem. Soc., Chem. Commun. 1993, 1118, incorporated herein by reference. This convergent strategy has also been employed by others to accomplish similar couplings, e.g., Di Grandi et al., J. Org. Chem. 1993, 58, 4989 and Maskers et al., Tetrahedron Lett. 1993, 34, 7253.
When synthesizing complex molecules, convergent strategies are often preferred over linear synthetic schemes because the overall yield can be significantly greater for the convergent strategy as compared to linear strategies. This advantage results from the fact the convergent scheme employs multiple starting points and generally fewer steps between each such starting point and the final product.
Although the above convergent strategy for the synthesis of taxol has been shown to be superior to linear schemes, the total length of the scheme remains significant and impairs its value as a commercial route to taxol. What are needed are taxoids and taxoid analogs which share structural and functional similarity with taxol but which are more readily accessible by convergent synthesis.